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Mol Cell Biol, July 1998, p. 4012-4022, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Adenovirus E1B 19,000-Molecular-Weight Protein Activates
c-Jun N-Terminal Kinase and c-Jun-Mediated Transcription
Raymond H.
See and
Yang
Shi*
Department of Pathology, Harvard Medical
School, Boston, Massachusetts 02115
Received 29 January 1998/Returned for modification 17 March
1998/Accepted 27 April 1998
Adenovirus E1B proteins (19,000-molecular-weight [19K] and 55K
proteins) inhibit apoptosis and cooperate with adenovirus E1A to induce
full oncogenic transformation of primary cells. The E1B 19K protein has
previously been shown to be capable of activating transcription;
however, the underlying mechanisms are unclear. Here, we show that
adenovirus infection activates the c-Jun N-terminal kinase (JNK) and
that the E1B gene products are necessary for adenovirus to activate
JNK. In transfection assays, we show that the E1B 19K protein is
sufficient to activate JNK and can strongly induce c-Jun-dependent
transcription. Mapping studies show that the C-terminal portion of E1B
19K is necessary for induction of c-Jun-mediated transcription. Using
dominant-negative mutants of several kinases upstream of JNK, we show
that MEKK1 and MKK4, but not Ras, are involved in the induction of JNK
activity by adenovirus infection. The same dominant-negative kinase
mutants also block the ability of E1B 19K to induce c-Jun-mediated
transcription. Taken together, these results suggest that E1B 19K may
utilize the MEKK1-MKK4-JNK signaling pathway to activate
c-Jun-dependent transcription and demonstrate a novel,
kinase-activating activity of E1B 19K that may underlie its ability to
regulate transcription.
*
Corresponding author. Mailing address: Department of
Pathology, Harvard Medical School, Warren Alpert Building, Room 120, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-4318. Fax: (617)
432-1313. E-mail: yshi{at}warren.med.harvard.edu.
Mol Cell Biol, July 1998, p. 4012-4022, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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